Rationale for early treatment initiation of AD during infancy

AD is not a stand-alone disorder, but is associated with a variety of comorbidities, including progression of atopic manifestations, known as the atopic march. Although results on the existence of a sequential atopic march have been inconsistent, a growing body of evidence supports that children with AD are at high risk of developing various atopic comorbidities including food allergy, asthma, and allergic rhinitis (24-31). The most apparent association is found between AD and sensitization to food allergens (24, 27, 28, 31). The mechanism behind the increased susceptibility to food allergy in patients with AD remains to be deciphered and is multifactorial, such as the pathogenesis of AD itself (28, 31, 32). Regardless of the mechanism, earlier onset and more severe disease are important risk factors for the development of usually multiple food allergies, arguing for preventative treatment strategies of AD during infancy (27, 33, 34). To address this hypothesis, a recent multicenter, randomized controlled trial (RCT), including 1,394 newborns, assessed the impact of daily emollient use during the first year of life to prevent AD as well as food allergy and other atopic comorbidities (35). Unlike other reports, emollients were not able to prevent AD, indicating that more effective treatment options may be needed to restore the skin barrier in infants who are at high risk to develop AD and subsequent atopic comorbidities (35).
The classical course of the atopic march, which progresses from AD to food allergy, allergic rhinitis, and ultimately asthma, has been challenged over the years. However, there is an undoubtable association between these atopic comorbidities, as already has been discussed for AD and food allergy. Although not every child with AD will be sensitized to inhalant allergens, several birth cohort studies have demonstrated that onset of AD during infancy, AD severity, and parental atopy are strong predictors to develop allergic rhinitis and asthma later in life (12, 25, 26, 36). The German Multicenter Allergy Study (MAS) is until now the longest birth cohort study, which followed up patients until the age of 20 years (26, 36). The MAS demonstrated that AD, asthma, and allergic rhinitis particularly coexist as a multimorbidity in patients who have parents with allergies, implying the importance of yet to be fully determined genetic factors (26, 37). More longitudinal studies are still warranted to understand if treatment at first signs and symptoms during infancy may prevent the allergic multimorbidity, especially in those who are at risk to develop atopy.
Additionally, AD was found to be associated with comorbidities beyond the atopic march, including cardiovascular and neuropsychiatric disorders (38-40). The latter comorbidity is mostly driven by the impact of AD on the whole family, particularly so on the QoL of young children and their caregivers (2, 38, 41). Itching and scratching are the most distressing early symptoms of the disease, which can lead to sleeplessness, psychological disorders, social isolation, and overall poor QoL of patients and their families (3, 42). Similar to atopic comorbidities, QoL decreases when the severity of AD increases, emphasizing the need for treatments that rapidly and sustainably relief pruritus (2).
There is also a considerable economic impact of AD on patients, patients’ families, and payers. Direct costs of AD are mostly related to prescriptions, physician visits, hospital costs, and pharmacy costs (2). These direct costs were calculated to be as high as \euro927 per patient per year by a recent cross-sectional study performed in nine European countries, and pose a significant economic burden to the patient that is more pronounced compared with other chronic diseases, such as psoriasis and rheumatoid arthritis (43). Furthermore, AD is associated with a variety of indirect costs due to decreased productivity and work absenteeism, which are a related to the social and psychological burden of the disease (2, 44). Paradoxically, the prevalence of AD was reported to correlate with the socioeconomic status, whereas patients with severe AD were found to have less educational attainment resulting in a lower annual income (44, 45). Consequently, improved care for AD would allow substantial savings on the short- and long-term for both patients and the society. Therefore, early treatment of AD is not only essential in treating the skin disease itself to prevent worsening, but also to prevent the development of atopic comorbidities and most importantly decrease the significant burden of AD on the entire family and the society as early as possible.